Memory for the News: Does Event Transience Matter?

BACKGROUND: Health providers frequently probe patients' recall of current and/or remote news events to determine the extent of memory loss. Impaired memory for transient events (ie, in the news for a circumscribed time) may provide information regarding the onset of cognitive impairment. OBJECTIVE: To use the Transient News Events Test (TNET) to explore how memory changes over time in both older adults with cognitive impairment (CI) and noncognitively impaired (NCI) older adults. We also investigated the role of episodic and semantic memory on TNET performance. METHOD: Sixty-seven older adults completed the TNET as part of a comprehensive neuropsychological assessment. Analyses included t tests to evaluate group differences for TNET score and correlations between TNET and neuropsychological measures, including episodic and semantic memory tests. RESULTS: NCI adults demonstrated better memory for TNET items than adults with CI. The NCI and CI groups did not differ regarding memory for remote events; however, the CI group exhibited worse memory for recent events. There was a significant association between TNET score and the capacity for episodic and semantic memory in the CI group. In the NCI group, TNET score was significantly associated with episodic memory. CONCLUSION: Findings support the use of transient news events to assess remote memories in older adults. Novel remote memory measures broaden the scope of memory assessment far beyond what is feasible with traditional neuropsychological assessment and may provide insight into the onset of memory changes.

Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging.

BACKGROUND: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. OBJECTIVE: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). METHODS: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. RESULTS: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls ( p < 10-2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only ( p < 10-2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume ( p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM ( p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. CONCLUSION: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.

Neuroinflammatory component of gray matter pathology in multiple sclerosis.

OBJECTIVE: In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. METHODS: Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent 11 C-PBR28 MR-PET. MS subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation. 11 C-PBR28 binding was measured using normalized 60- to 90-minute standardized uptake values and volume of distribution ratios. RESULTS: Relative to controls, MS subjects exhibited abnormally high 11 C-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, 11 C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased 11 C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels. INTERPRETATION: In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790.

Is the Relationship between Cortical and White Matter Pathologic Changes in Multiple Sclerosis Spatially Specific? A Multimodal 7-T and 3-T MR Imaging Study with Surface and Tract-based Analysis.

PURPOSE: To investigate in vivo the spatial specificity of the interdependence between intracortical and white matter (WM) pathologic changes as function of cortical depth and distance from the cortex in multiple sclerosis (MS), and their independent contribution to physical and cognitive disability. MATERIALS AND METHODS: This study was institutional review board-approved and participants gave written informed consent. In 34 MS patients and 17 age-matched control participants, 7-T quantitative T2* maps, 3-T T1-weighted anatomic images for cortical surface reconstruction, and 3-T diffusion tensor images (DTI) were obtained. Cortical quantitative T2* maps were sampled at 25%, 50%, 75% depth from pial surface. Tracts of interest were reconstructed by using probabilistic tractography. The relationship between DTI metrics voxelwise of the tracts and cortical integrity in the projection cortex was tested by using multilinear regression models. RESULTS: In MS, DTI abnormal findings along tracts correlated with quantitative T2* changes (suggestive of iron and myelin loss) at each depth of the cortical projection area (P < .01, corrected). This association, however, was not spatially specific because abnormal findings in WM tracts also related to cortical pathologic changes outside of the projection cortex of the tract (P < .001). Expanded Disability Status Scale pyramidal score was predicted by axial diffusivity along the corticospinal tract (ß = 4.6 × 10(3); P < .001), Symbol Digit Modalities Test score by radial diffusivity along the cingulum (ß = -4.3 × 10(4); P < .01), and T2* in the cingulum cortical projection at 25% depth (ß = -1.7; P < .05). CONCLUSION: Intracortical and WM injury are concomitant pathologic processes in MS, which are not uniquely distributed according to a tract-cortex-specific pattern; their association may reflect a common stage-dependent mechanism.

Subjective Cognitive Complaints in Concussion.

Studies of symptoms after concussion have been focused heavily on athletic and military populations; generalizability to "civilians" has not recently been demonstrated. We selected cognitive symptoms as an important target to assess because of impact on school and employment. We evaluated cognitive complaints in a highly symptomatic (Rivermead Post-Concussion Symptoms Questionnaire [PCSQ], mean [M] = 29.5) civilian sample (n = 100; age: M = 41.4; 36 male/64 female; days post-injury: range 14-154, M = 51.4) of consecutive referrals to a concussion specialty clinic. The Behavior Rating of Executive Functions-Adult version (BRIEF-A) was used to assess subjective cognitive symptoms. Independent variables were prior neurologic and psychiatric history, current neurological symptoms, objective neuropsychological tests and several measures of depression (Beck Depression Inventory, Second Edition [BDI2]), anxiety (Beck Anxiety Inventory), and stress (Post-Traumatic Stress Checklist-Civilian form). No demographic characteristic, injury measure, or past or current neurological history had any association with cognitive symptoms. Prior psychiatric history (57% of patients) was associated with abnormal BRIEF-A. Cognitive tests were overall in the average range, with only mild and sporadic associations with BRIEF-A elevations. All psychological measures showed significant associations with BRIEF-A elevations. Regression analyses for the BRIEF-A revealed depression was the significant contributor (BDI2, ß = 0.73) with prior psychiatric history (ß = 0.16) and age (ß = 0.14) accounting to a lesser extent. In this civilian cohort, subjective cognitive symptoms appear to be due to psychological distress (in particular, depression) and prior psychiatric history more than actual cognitive impairment or other presenting symptoms. These findings illuminate the importance of early diagnosis and treatment of mood/emotional symptoms after injury.

Concussion: Evaluation and management.

Concussion is a common problem often managed by nonneurologists. It is often accompanied by headaches, dizziness, sleep disturbance, psychiatric symptoms, and cognitive issues. Here, we outline how to evaluate and manage concussion, including treatment of the most common symptoms.

The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T2* mapping at 7 T MRI.

Using quantitative T2* at 7 Tesla (T) magnetic resonance imaging, we investigated whether impairment in selective cognitive functions in multiple sclerosis (MS) can be explained by pathology in specific areas and/or layers of the cortex. Thirty-one MS patients underwent neuropsychological evaluation, acquisition of 7 T multi-echo T2* gradient-echo sequences, and 3 T anatomical images for cortical surfaces reconstruction. Seventeen age-matched healthy subjects served as controls. Cortical T2* maps were sampled at various depths throughout the cortex and juxtacortex. Relation between T2*, neuropsychological scores and a cognitive index (CI), calculated from a principal component analysis on the whole battery, was tested by a general linear model. Cognitive impairment correlated with T2* increase, independently from white matter lesions and cortical thickness, in cortical areas highly relevant for cognition belonging to the default-mode network (p < 0.05 corrected). Dysfunction in different cognitive functions correlated with longer T2* in selective cortical regions, most of which showed longer T2* relative to controls. For most tests, this association was strongest in deeper cortical layers. Executive dysfunction, however, was mainly related with pathology in juxtameningeal cortex. T2* explained up to 20% of the variance of the CI, independently of conventional imaging metrics (adjusted-R2: 52-67%, p < 5.10- 4). Location of pathology across the cortical width and mantle showed selective correlation with impairment in differing cognitive domains. These findings may guide studies at lower field strength designed to develop surrogate markers of cognitive impairment in MS.

Quantitative oxygen extraction fraction from 7-Tesla MRI phase: reproducibility and application in multiple sclerosis.

Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2*-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of ~10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV)=2.1%, interobserver COV=5.2%, and scan-rescan COV=5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls (P=0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS.

Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS.

OBJECTIVES: Evaluate cross-sectionally the contribution of focal cortical lesion (CL) subtypes at ultra-high-field MRI and traditional MRI metrics of brain damage to neurologic disability and cognitive performance in a heterogeneous multiple sclerosis (MS) cohort. METHODS: Thirty-four patients with early or established disease including clinically isolated syndrome, relapsing-remitting MS, and secondary progressive MS were scanned on a human 7-tesla (7T) (Siemens) scanner to acquire fast low-angle shot (FLASH) T2*-weighted images for characterization of white matter and deep gray matter lesion volume, and CL types. Patients also underwent anatomical 3T MRI for cortical thickness estimation, and neuropsychological testing within 1 week of the 7T scan. Twenty-seven patient scans were acceptable for further analysis. Neurologic disability was measured using the Expanded Disability Status Scale. RESULTS: Type III-IV CLs had the strongest relationship to physical disability (ρ = 0.670, p < 0.0001). White matter lesion volume and type I CLs are each significantly associated with 6 of 11 neuropsychological test variables. Type III-IV CLs significantly correlate with 4 of 11 neuropsychological test variables whereas type II CLs, deep gray matter lesion volume, and cortical thickness metrics are less frequently associated with cognitive performance. CONCLUSIONS: Leukocortical (type I) and subpial (III-IV) CLs identified on 7T FLASH-T2* sequences are potential cortical biomarkers of cognitive and neurologic status in MS.